RRC ID |
50647
|
Author |
Kitadani J, Ojima T, Iwamoto H, Tabata H, Nakamori M, Nakamura M, Hayata K, Katsuda M, Miyajima M, Yamaue H.
|
Title |
Cancer Vaccine Therapy Using Carcinoembryonic Antigen - expressing Dendritic Cells generated from Induced Pluripotent Stem Cells.
|
Journal |
Sci Rep
|
Abstract |
Clinical application of dendritic cell (DC) vaccine therapy is hindered by the need for a large quantity of DCs generated from peripheral blood monocytes of the patient. We investigated whether genetically modified human induced pluripotent stem cell (iPSC)-derived dendritic cells (hiPSDCs) expressing carcinoembryonic antigen (CEA) could induce CEA-specific cytotoxic T cells in a human model and whether genetically modified mouse iPSDCs (miPSDCs) expressing CEA showed an actual antitumor effect using a CEA transgenic mouse model. We differentiated hiPSDCs from iPSCs of three healthy donors and transduced CEA cDNA into the hiPSDCs. The surface marker expression, cytokine secretion and migratory capacity of the hiPSDCs were equivalent to those of human monocyte-derived DCs (hMoDCs). Cytotoxic T cells activated by hiPSDCs-CEA exhibited CEA-specific cytotoxic activity against the target cells expressing CEA. Furthermore, in the CEA transgenic mouse model, cytotoxic T cells activated in mice immunized with miPSDCs-CEA displayed CEA-specific cytotoxic activity against MC38-CEA. In the subcutaneous tumour model, vaccination with miPSDCs-CEA achieved a significant growth inhibitory effect on MC38-CEA. No adverse events caused by the administration of miPSDCs were observed. Genetic modification of iPSDCs, inducing the expression of CEA, is a promising tool for clinical applications of vaccine therapy for treating gastrointestinal cancer patients.
|
Volume |
8(1)
|
Pages |
4569
|
Published |
2018-3-15
|
DOI |
10.1038/s41598-018-23120-z
|
PII |
10.1038/s41598-018-23120-z
|
PMID |
29545628
|
PMC |
PMC5854614
|
MeSH |
Animals
Cancer Vaccines / immunology*
Carcinoembryonic Antigen / genetics
Carcinoembryonic Antigen / immunology
Carcinoembryonic Antigen / metabolism*
Cells, Cultured
Dendritic Cells / cytology
Dendritic Cells / metabolism*
Dendritic Cells / transplantation
Humans
Induced Pluripotent Stem Cells / cytology*
Interferon-gamma / metabolism
Interleukin-12 / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Skin Neoplasms / immunology
Skin Neoplasms / pathology
Skin Neoplasms / prevention & control*
Spleen / cytology
T-Lymphocytes, Cytotoxic / immunology
|
IF |
3.998
|
Times Cited |
7
|
Resource |
Human and Animal Cells |
iPS-MEF-Ng-20D-17(APS0001) |